Department of Genetics and Laboratory Medicine, Credit Valley Hospital, Mississauga, Ontario, Canada.
Am J Med Genet B Neuropsychiatr Genet. 2011 Jun;156B(4):484-9. doi: 10.1002/ajmg.b.31186. Epub 2011 Apr 7.
Protocadherin11 is located on both the X and Y chromosomes in Homo sapiens but only on the X chromosome in other hominid species. The pairing of PCDH11Y with PCDH11X arose following a duplicative 3.5 Mb translocation from the ancestral X chromosome to the Y chromosome several million years ago. The genes are highly expressed in fetal brain and spinal cord. The evolutionary consequence of this duplication has been proposed to include the sexual dimorphism of cerebral asymmetry and the hominid specific transition to the capacity for language. We report a case of a male child referred for genetic investigation of severe language delay. Microarray analysis indicated the presence of a 220 Kb intragenic deletion at Xq21.31 involving the PCDH11X gene. Fluorescence in situ hybridization using a BAC probe mapping to intron 2 of the Protocadherin11X/Y gene pair confirmed loss of the locus on both the X and Y chromosomes. The X chromosome deletion was maternally inherited, but the Y chromosome deletion was found to be a de novo occurrence in this child. This finding lends support to the hypothesis that the Protocadherin11X/Y gene plays a role in language development in humans and that rare copy number variation is a possible mechanism for communication disorders.
原钙黏蛋白 11 位于智人物种的 X 和 Y 染色体上，但在其他人类物种中仅位于 X 染色体上。PCDH11Y 与 PCDH11X 的配对是在几百万年前，从祖先 X 染色体到 Y 染色体的重复 3.5Mb 易位后产生的。这些基因在胎儿大脑和脊髓中高度表达。这种重复的进化后果被认为包括大脑不对称的性别二态性和人类特有的语言能力的转变。我们报告了一名男性儿童的病例，该儿童因严重语言延迟接受遗传调查。微阵列分析表明，Xq21.31 存在涉及 PCDH11X 基因的 220kb 内含子缺失。使用映射到原钙黏蛋白 11X/Y 基因对内含子 2 的 BAC 探针的荧光原位杂交证实了该基因在 X 和 Y 染色体上的缺失。X 染色体缺失是母系遗传的，但 Y 染色体缺失被发现是该儿童的新发事件。这一发现支持了原钙黏蛋白 11X/Y 基因在人类语言发育中发挥作用的假说，并且罕见的拷贝数变异是一种可能的通信障碍机制。
